Anti-rheumatic mixture and method of preparing



2,790,746 ANTI-RHEUMATIC MIXTURE ANDMETH'OD'OF PREPARING Paulo Seabra, Rio de JaneirmBra'iil, assignor to Souza, Seabra & Cia; Ltdm, Rio' de Janeiro, F. D., Brazil, a corporation of Brazil No Drawing. Application-Ianua'ry 29,- 1954, Serial N0. 407,158

8 Claims. (Cl; 1'67--64) This invention relates to an anti-rheumatic mixture. The use of cortisone and other hormones'i'n the treatment of rheumatism has been' questioned due to the effect of such hormones'on'active and apparently inactive tuberculosis, occasioning arevival of interest in salicylates as a treatment for rheumatism. As a matter of fact, it has been shown that cortisone andother hormones act inthe same manner as othersalicylates on rheumatic tissue by inactivating hyaluronidase.

However, the conventional salicylate treatment has many disadvantages. For example, tests have shown that the intravenous administration of salicylates has no superiority over the oral administration, resulting in the adopthe affected tissues is animportantfactor in the production of pain and impairment of motion, and that the therapy indicated is therefore that of inducing dehydration. In the intricate bio-chemistry of edema,- rigorous :analysis of urine sampleshas' shown; a" constant retention of sodium that varies directly with the severity of the illness. Patients with hepatic cirrhosis have shown great :sodium reduction in their urine, some presenting only traces. Other studies have shown that during the acute stage of the rheumatic, at the moment of polyarthritis, a decrease in sodium chloride in the urine has been noted. Therefore, the rheumatic patient may be subjected to the discomfort of a lower salt diet which according to certain authorities is effective only if the total nyctohemeril intake is less than one gram of salt. Consider then the error of treating the patient at the same time with six, eight or sixteen grams of another compound, namely, the salicylate, which carries in these doses respectively two, three and six times more sodium, the edema inducing metal.

Instead of administering sodium salts of the salicylate, it has been proposed to employ instead the calcium salts, since sodium and calcium are ionic antagonists in all physiological reactions. In fact, it has been demonstrated that the increase of sodium in relation to calcium is occasioned by the afilux of water from the serum to the tissues. It has been shown that the serologic relation of sodium to calcium (its normality being 33) increases in the edematous patient, either due to the excess of sodium or lack of calcium, as may be seen from the following table:

Serologic relation sodium to calcium 2,790,746 te ear 3? It has also been demonstrated that the diuretic action is exercised by calcium salts independent of the acid with which it is combined. Calcium, when mobilizing the liquidof articular edemas is very often accompanied with slight pain exacerbation, which usually occurs also with the use of radio therapy, cortisone, and corticotropin. One authority, administering calcium in combination with a weak acid, i. e., calcium gluconate, observed acute exacerbation followed soon by remission, effecting complete cure in twenty-three cases of acute rheumatism and twenty-eight of chronic rheumatism, restoring articular mobility, normalizing the erythrocytic sedimentation, and showing cardiac improvement without relapse during one year of observation. This authority attributes great importance to the desensitizing role also performed by the calcium.

From the foregoing it will be quite clear that in the salicylate treatment of rheumatism that salicylic acid and calcium are beyond question the indicated drugs. However, the problem resides in the administration; in attempting to have the salicylic acid reach the arterial blood the salicylic acid is fixed by the cartilagenous tissue with astonishing selectivity. However, it has been shown that a very small dose of salicylate is sufficient if it reaches the arterial blood, because while such a dose is small when compared with the total weight of the body, itis no longer as small when compared only with the weight of the cartilage, which also is small. When administered orally in small closes, the salicylic acid does not reach the arteries because it is detained by the liver. In fact, the salicylate effects a special hepato-toxic action on the liver, which further accentuates the unfavorable effects produced by the rheumatismal disease. Thefirst thing the salicylate does when it reaches the liver is to paralyze the glycogenesis in the already damaged liver. Thus, a struggle is drawn between the liver and the salicylate, which latter is administered daily in ever increasing doses up to six, eight and sixteen grams in the hope that a small portion reaches the arteries while the liver is being increasingly damaged.

It is accordingly a principal object of the present invention to provide an anti-rheumatic mixture effective in the treatment of rheumatism wherein the small and effective dose of salicylate required is introduced into the arterial blood without passing through the liver.

It is another object of the present invention to provide an anti-rheumatic mixture of the above type which is administered in the form of a suppository.

It is still another object of the present invention to provide an anti-rheumatic mixture of the above type wherein the active principle is absorbed during rectal administration by the inferior hemorrhoidal plexus, the

principal then passing to the median and inferior hemorrhoidal veins and reaching the heart without passing through the liver.

Other objects and the advantages and nature of my improved anti-rheumatic mixture will be apparent from the following description of the ingredients making up the same, the proportions thereof, the method of preparation and the manner in which the aforesaid anti-rheumatic mixture is to be used.

My improved formula for making the anti-rheumatic mixture contains the following thoroughly admixed i11- gredients: Salicylic acid, calcium carbonate and an inactive base to insure the necessary consistency of a suppository.

I have found that a mixture of salicylic acid calcium carbonate and polyethylene glycol yields the best results, although mixtures containing other inert bases in place of polyethylene glycol may also be used.

I prefer to make up the above described mixture in the following proportions:

24 parts by weight of salicylic acid 8 parts by weight of calcium carbonate 160 parts by weight of polyethylene glycol The above proportions of my mixture may be considerably varied without effecting its efliciency and the above proportions are set forth merely to illustrate a formula that I have found to work well in practice.

The mixture is prepared by thoroughly mixing 24 parts by weight of salicylic acid and 8 parts by weight of calcium carbonate. To the resulting powder, 160 parts of polyethylene glycol are added in a mechanical homogenizeru The resulting mixture is placed in a sterilizer and heated to 120 degrees C. for a half hour, care being taken to permit the escape of any gas that is formed.

Tests have shown that this anti-rheumatic mixture when administered in the form of a suppository spares the liver and introduces the small but effective dose of salicylate in the arterial blood, the active principle being absorbed by the inferior hemorrhoidal plexus, passing through the median and inferior hemorrhoidal veins and finally reaching the heart without passing through the liver. The anti-rheumatic quality of this mixture results from the calcium salicylate formed in the mixture.

While various changes'may be made in the detailed composition and proportions of my mixture, it should be understood that such changes shall be within the spirit and scope of the invention as defined by the appended claims.

I claim:

1. An anti-rheumatic suppository comprising as the basic ingredients an inert substance having the necessary consistency of a suppository, and calcium salicylate.

2. An anti-rheumatic suppository comprising as the basic ingredients an inert substance having the necessary consistency of a suppository, and calcium salicylate, said inert substance consisting of polyethylene glycol.

3. An anti-rheumatic mixture comprising an inert substance having the necessary consistency of a suppository, and calcium salicylate.

4. An anti-rheumatic mixture comprising an inert substance having the necessary consistency of a suppository, and calcium salicylate, said inert substance consisting of polyethylene glycol.

5. An anti-rheumatic mixture comprising an inert substance having the necessary consistency of a suppository, and calcium salicylate, said inert substance consisting of polyethylene glycol, said mixture being prepared by mixing the following ingredients in the following proportions by weight: 24 parts salicylic acid, 8 parts calcium carbonate and 160 parts of inactive substance.

6. A method of preparing an anti-rheumatic suppository comprising mixing salicylic acid and calcium carbonate, adding to the resultant mixture an inert substance having the necessary consistency of a suppository and thoroughly admixing the same, sterilizing the resultant mixture at about degrees C. for approximately a half hour and permitting the evolved gases to escape.

7. A method of preparing an anti-rheumatic suppository comprising thoroughly admixing 24 parts by weight of salicylic acid and 8 parts by weight of calcium carbonate, adding to the resultant mixture parts by weight of an inert substance having the consistency of a suppository and thoroughly admixing the same, sterilizing the resulting mixture at about 120 degrees C. for a half hour and permitting the evolved gases to escape.

8. The process according to claim 7, wherein the inert substance is polyethylene glycol.

References Cited in the file of this patent UNITED STATES PATENTS 2,471,394 Gubner May 24, 1949 FOREIGN PATENTS 689,722 Great Britain Apr. 1, 1953 OTHER REFERENCES Coblentz: The Newer Remedies, 3rd ed., 1899, p. 36, Phila, Blackistons Son.

Gross: Jour. Am. Pharm. Assoc., vol. XLII, No. 2, Feb. 1953, pp. 90-95. 

1. AN ANTI-RHEUMATIC SUPPOSITORY COMPRISING AS THE BASIC INGREDIENTS AND INERT SUBSTANCE HAVING THE NECESSARY CONSISTENCY OF A SUPPOSITORY, AND CALCIUM SALICYLATE. 